tbuckley/cabot-search huggingface dataset:
Phase II trial of split-dose R-CHOP for older patients with diffuse large B-cell lymphoma (DLBCL).
Authors: Nirav Niranjan Shah, Aniko Szabo, Saurabh Rajguru, Sumana Devata, Mitch Howard, Deepa Pereira, Mariah Endres, Walter L. Longo, Mehdi Hamadani, Timothy S. Fenske, Christopher David Fletcher
Journal: Journal of Clinical Oncology (2023)

7554 Background: Management of elderly DLBCL is limited by age associated comorbid conditions and decreased tolerance of chemotherapy regimens. Many elderly or unfit/frail patients (pts) with DLBCL receive either non-anthracycline based treatment (tx) or attenuated regimens such as Rituximab (R)-miniCHOP which is ~50% dose reduction from standard R-CHOP-21. Split-dose (SD) R-CHOP is an alternative approach where pts receive CHOP at a 50% dose reduction on Days 1 and 15 of each 28-day cycle with full dose Rituximab on Day 1 for 6 cycles. The cumulative dose of SD R-CHOP delivered over each 28 day cycle is equivalent in dose intensity to one cycle of standard R-CHOP-21. Methods: This is a Phase II, prospective, open label study conducted through the Wisconsin Oncology Network and included two academic centers (NCT03943901). Older pts aged≥75 years or 70-74 years plus elevated cumulative illness rating scale for geriatrics score with untreated de-novo or transformed Stage IIX-IV DLBCL were eligible. Treatment consisted of two months (4 doses) of SD R-CHOP with growth factor support followed by interim response assessment with PET/CT and peripheral blood cell-free clonoSEQ minimal residual testing (MRD). Pts with interim PET/CT score of Deauville 1-3 and MRD negativity were offered abbreviated therapy with two additional months of SD-R-CHOP. All others completed 6 cycles. The primary endpoint was end of tx (EOT) complete response (CR) rate. We utilized a Simon 2-stage design with interim analysis requiring at least 8 EOT CR in the first 16 pts (Stage I) to proceed to stage II. Results: To date, 14 pts have completed tx. The median age was 81 years (73-88) and 57% (n = 8) were male. Most pts had stage 4 disease (n = 8, 57%). 8 of 14 pts were interim PET/CT negative and 8 of 12 MRD evaluable pts were interim MRD negative. 10/14 (71%) pts achieved EOT CR exceeding our minimal threshold to continue the study early. The remaining 4 pts had progressive disease (PD) either during tx or at EOT evaluation. 6 pts were both interim MRD and PET negative; 5 de-escalated to the abbreviated arm with all achieving CR with no relapses to date. 7 pts (50%) had Grade 3+ non-hematologic toxicities and 4 pts (29%) had Grade 3-4 neutropenia. There were 2 deaths, one from COVID-19 with concurrent PD and the other from PD. Median PFS or OS have not been reached with a median follow-up of 13 months for surviving pts. Conclusions: SD-R-CHOP offers older pts with DLBCL equivalent dose intensity as R-CHOP-21 through a fractionated dosing schedule improving tolerability. Prespecified interim efficacy endpoint was met early with 10/14 pts with EOT CR. Interim stratification by MRD and PET/CT allowed de-escalation of tx in early responding pts without compromising efficacy. Clinical trial information: NCT03943901 . [Table: see text]
Incidence and outcomes of immune-related adverse events after immune checkpoint inhibitors in patients with Hodgkin lymphoma.
Authors: Cindy (Hsin-Ti) Lin, William W. Tse, Jiasheng Wang
Journal: Journal of Clinical Oncology (2023)

e19513 Background: Immune checkpoint inhibitors (ICIs) have recently been found to be effective in Hodgkin lymphoma (HL). However, given the impaired systemic immune response in HL, it is unclear whether immune-related adverse events (irAEs) would manifest differently in this population; data on this topic remains scarce. Methods: Data were collected from an aggregated electronic medical record (EMR) database TriNetX Research Network (TriNetX LLC., Cambridge, Massachusetts, USA). Adult patients diagnosed with HL who received pembrolizumab or nivolumab between 1/2018 and 1/2022 were included. irAEs were identified through a set of validated ICD-10-CM codes. Results: Within the study period, a total of 567 patients with HL were identified. Among them, 363 (63.8%) patients received nivolumab and 263 (46.4%) received pembrolizumab. The mean age was 50.1 (SD 19.6) years-old, 227 (40.0%) patients were female, 69 (12.2%) were black, and 156 (27.5%) received ICI-based therapy as the frontline treatment. irAE of any grade occurred in 280 (49.4%) of patients. Patients who experienced irAEs were more likely to be older (p = 0.0106), while using ICIs as the frontline or after various previous treatments was not associated with irAEs (Table). Among specific irAEs, skin toxicities, thyroid dysfunction, pneumonitis, colitis, and hepatitis occurred in 31.6%, 23.6%, 2.8%, 9.3%, and 3.2% of patients, respectively. Regarding the management for irAEs, systemic steroids, topical steroids, mycophenolate, and infliximab were used in 63.6%, 36.8%, 3.6%, and 3.6% of patients, respectively. Of note, ICIs were able to be resumed in 71.1% of patients with irAEs. After propensity-score matching for known prognostic factors for HL, patients with or without irAE had similar overall survival (OS) (hazard ratio 0.84, 95% confidence interval 0.57 to 1.23, p=0.36). No significant difference of OS was seen across different subtypes of irAE, including skin toxicities (p=0.64), thyroid dysfunction (p=0.74), or colitis (p=0.28). Conclusions: irAEs were common in patients with HL receiving ICIs. The majority of patients with irAEs were able to resume ICIs, and the development of irAEs did not affect overall survival. [Table: see text]
Efficacy and safety of irinotecan-eluting HepaSphere transarterial chemoembolization combined with hepatic arterial infusion chemotherapy for unresectable colorectal liver metastases.
Authors: Aiwei Feng, Song Gao, Jianhai Guo, Fuxin Kou, Shaoxing Liu, Xin Zhang, Baojiang Liu, Xiaodong Wang, Hui Chen, Haifeng Xu, Peng Liu, Guang Cao, Qinzong Gao, Xu Zhu
Journal: Journal of Clinical Oncology (2023)

3585 Background: Both drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) are recommended for unresectable colorectal liver metastases (CRLM) treatment. However, the combined application of DEB-TACE and HAIC is not widely accepted. The aim of this single-center retrospective study was to evaluate the efficacy and safety of Irinotecan-eluting HepaSphere chemoembolization combined with HAIC for unresectable CRLM. Methods: Patients with age older than 18 years, histologically confirmed CRLM and treated with Irinotecan-eluting HepaSphere chemoembolization plus HAIC from Oct 2020 to Jan 2022 were enrolled. Patients who had synchronously received other local treatments were excluded. Hepatic progression-free survival (hPFS) and PFS were calculated using Kaplan-Meier method. Adverse events (AE) were evaluated with CTCAE 5.0. Results: The eligible population was 101, composed of 66 males and 35 females. Among them, 54% patients had one of KRAS or NRAS or BRAF gene mutation and ECOG of 62% patients was 1. In addition, 59% patients were refractory to second standard line or above systemic therapy and mean interventional treatment cycles were 3.3. As the follow-up cutoff date was Dec 31, 2022, median duration of follow-up was 17.9 months (95% CI,16.185-19.615). Median hPFS was 8.7 months (95% CI, 6.744-10.658) while median PFS was 6.2 months (95% CI, 5.048-7.352). For the patients who were refractory to second line or above systemic therapy, hPFS and PFS was 6.2 months (95% CI, 4.899-7.501) and 5.2 months (95% CI, 3.682-6.718) respectively. Overall survival has not been reached yet. There were 7 patients achieved clinical complete response. Overall response rate was 41.6% and disease control rate was 82.2%. There was no treatment-related death. 28 patients (27.7%) experienced grade 3 or higher toxicities. The most common treatment related AE were aspartate transaminase/alanine transaminase elevation (41.6%) and bilirubin elevation (40.6%). The hematologic AE included anemia (27.7%), leukopenia (27.7%), neutropenia (14.9%) and thrombocytopenia (28.7%). Conclusions: The combination of Irinotecan-eluting HepaSphere chemoembolization and HAIC is effective and safe for unresectable CRCLM, even for patients who are refractory to second or above systemic therapy, indicating it is a promising regional treatment with improved outcome.
Impact of acute kidney injury on overall survival in postoperative patients with head and neck cancer who received chemoradiotherapy with cisplatin: A supplementary analysis of a phase II/III trial of JCOG1008.
Authors: Yoshinori Imamura, Naomi Kiyota, Makoto Tahara, Takeshi Kodaira, Ryuichi Hayashi, Hiroshi Nishino, Yukinori Asada, Hiroki Mitani, Shigemichi Iwae, Naoki Nishio, Yusuke Onozawa, Nobuhiro Hanai, Akira Ohkoshi, Hiroki Hara, Nobuya Monden, Masato Nagaoka, Shujiro Minami, Ryo Kitabayashi, Keita Sasaki, Akihiro Homma
Journal: Journal of Clinical Oncology (2023)

6079 Background: A randomized phase II/III trial of JCOG1008 demonstrated that chemoradiotherapy (CRT) with weekly cisplatin at 40 mg/m 2 (Weekly arm) was noninferior to 3-weekly cisplatin at 100 mg/m 2 (3-weekly arm) in terms of overall survival (OS) for postoperative high-risk head and neck cancer (hazard ratio [HR], 0.69 [99.1% CI, 0.37 to 1.27 &lt; 1.32]; J Clin Oncol 2022; 40: 1980-90). Acute kidney injury (AKI) is a major dose-limiting toxicity of cisplatin. Here, we investigated the impact of AKI on OS in patients treated with CRT in JCOG1008. Methods: A total of 251 patients who were treated with CRT in JCOG1008 were analyzed. AKI was defined as an increase in serum creatinine of ≥0.3 mg/dL or a 1.5-fold or more increase from baseline (≥stage I) within 30 days after completion of CRT, based on the AKI Network classification/staging system. OS in the two arms was compared by the development of AKI using the log-rank test. Results: The total incidence of AKI in the weekly arm was lower than that in the 3-weekly arm (38 of 122 [31.1%] vs. 56 of 129 [43.4%]). The incidence of stage II/III AKI was also lower in the weekly arm (8 of 122 [6.6%] vs. 19 of 129 [14.7%]). Total cisplatin dose was similar in patients who did and did not develop AKI in the weekly arm, but was lower in patients who developed AKI in the 3-weekly arm (Table). Moreover, no difference in OS was observed between patients who did and did not develop AKI in the weekly arm (HR, 1.06 [95% CI, 0.53 to 2.10]), whereas patients who developed AKI in the 3-weekly arm had poorer OS than those who did not (HR, 1.83 [95% CI, 1.04 to 3.21]). Conclusions: In this supplementary analysis of JCOG1008, development of AKI impacted OS in the 3-weekly arm, but not in the weekly arm. Consistent exposure to cisplatin through weekly fractionated administration appears of greater clinical significance than cumulative dose, providing maintenance of treatment intensity and better kidney safety, and likely also improving outcomes. Clinical trial information: jRCTs031180135 . [Table: see text]
The predictive value of CA-125 for radiologic evidence of metastatic disease in type 2 endometrial cancers.
Authors: Madison Ellis Miller, Tra Pham, Monica Kole, Mohamed A. Elshaikh, Irina Dimitrova
Journal: Journal of Clinical Oncology (2023)

e17610 Background: Type 2 endometrial cancers encompass histologic variants that are more aggressive and have a higher incidence of extrauterine disease at the time of presentation than their type 1 counterparts. For high grade endometrial carcinomas, current National Comprehensive Cancer Network (NCCN) guidelines propose the "consideration of chest, abdomen and pelvis CT to evaluate for metastatic disease." We sought to investigate the predictive value of serum CA-125 for radiographic evidence of metastatic disease in patients with type 2 endometrial cancers. Methods: An IRB-approved, retrospective study investigating patients diagnosed with endometrial cancers between 2000-2020 at an urban, multi-site health system was conducted. Only patients with type 2 endometrial cancers and both pre-operative computed tomography scans of the chest, abdomen, and pelvis (CT CAP) and serum CA-125 results were included. A Youden’s index was used to calculate the optimal CA-125 cutoff. The sensitivity and specificity of CA-125 in predicting radiographic evidence of extrauterine disease was then calculated using this pre-determined CA-125 cutoff. Results: In total, 2,227 patients diagnosed with endometrial cancer (types 1 and 2) between 2000-2020 were identified. 1,932 cases were excluded due to low grade disease and/or the absence of pre-operative imaging and CA-125 results. Ultimately, 295 cases were included in analyses. A receiver operating characteristic (ROC) curve was used to generate Youden’s index which established the optimal CA-125 cutoff as 68 U/mL (P=0.0005). Using this cutoff, the specificity and sensitivity were determined to be 92.45% and 63.86%, respectively. The positive predictive value was 76.81% and the negative predictive value was 86.73%. Conclusions: According to current NCCN guidelines, pre-operative imaging and CA-125 should be considered if extrauterine disease is suspected in the setting of endometrial cancer. Although the role of serum CA-125 in monitoring clinical response is well documented, the utility of this test in stratifying patients who should undergo further radiologic evaluation is uncertain. Our results suggest that a CA-125 cutoff of &gt; 68 U/mL is predictive of radiographic evidence of metastatic disease and, thus, can be used to determine which patients should receive pre-operative CT CAP.
Intraarterial chemotherapy of liver metastases of colorectal cancer. Experience of National Cancer Institute of Ukraine.
Authors: Veronika Patsko, Andrii Lukashenko, Yuriy Ostapenko
Journal: Journal of Clinical Oncology (2023)

e15619 Background: Liver - is the most often site of colorectal cancer metastases. Although surgical resection of primary tumor and liver metastases is the most radical type of treatment, only 10-25% of patients are eligible for this approach. Our aim was to evaluate efficacy of intraarterial chemotherapy for patients with primary unresectable metastatic colorectal cancer (mCRC) to improve prognosis and overall response for treatment. Methods: records of 73 patients with primary unresectable mCRC, who undergone catheterization of liver artery and received intraartetial chemotherapy (with 5-FU) in period 2008-2018 years at the Clinic of National Cancer Institute (Ukraine). Results: the figure of overall response: 57.5% (n = 42) - partial response, 8.2% (n = 6) - complete radiological response, 12.3% (n = 9) - stable disease, 21.9% (n = 16) - chemoresistant tumor. 46.6% (n = 34) of patient undergone resection of previously unresectable liver metastases. In 4.1% (n = 3) complete histological response was estimated. Surgical mortality and morbidity rate were 1.3% and 6.8% respectively. Cause of postoperative mortality was lung embolism, complications included bacterial infections and hemorrhage in postoperative period. Main reason for inability to perform operations were post chemotherapeutic toxicity, which did not resolved on optimal terms for operation. The overall 5-year survival rate was 29.4% in group who undergone resection and 17.9% in group, were patients were not radically operated (p &lt; 0.05). Conclusions: catheterization of liver artery with further intraarterial chemotherapy can potentially convert unresectable metastases into resectable, therefore improving treatment results and overall survival.
Impact of WNT/B-catenin alterations and metastasis location among patients with metastatic colorectal cancer (mCRC) treated with immune checkpoint inhibitors (ICI) combinations.
Authors: Javier Ros Montañá, Iosune Baraibar, Victor Navarro Garces, Nadia Saoudi Gonzalez, Sharela Vega, Sergio Bueno, Ariadna Garcia, Francesc Salva, Raquel Comas, Marta Rodríguez Castells, Omar Saavedra, Guzman Alonso, Elena Garralda, Josep Tabernero, Ana Vivancos, Elena Elez
Journal: Journal of Clinical Oncology (2023)

3573 Background: Emerging evidence suggests that WNT mutations and liver/peritoneal metastases in mCRC may have an immunosuppressive role that could affect ICI activity. Aim: To evaluate the impact of WNT alterations and liver/peritoneal metastasis among patients with mCRC treated with ICi. Methods: Patients from Vall d’Hebron Hospital, with mCRC treated with ICI from 2017-2022 were included. WNT alterations (APC, AXIN1/2, CTNNB1, FBXW7, EPHB2, RNF43 and SOX9) were evaluated using NGS (tissue). Clinical outcomes were calculated using survival Kaplan-Meier curves. Patients' characteristics were collected retrospectively. Results: Overall, 104 patients were included (66 MSI patients and 38 MSS patients). Among MSI patients, median age was 63 years (22-95), with 53% female, and 64% of patients received immunotherapy in 1st or 2nd line. Regarding tumor characteristics, 72% were right-sided and 82% harbored WNT alterations. 75% of patients presented with liver/peritoneal metastases. Patients with WNT mutations and peritoneal/liver metastases exhibit lower ORR (46% vs 57% p 0.5 and 45% vs 75%, p 0.03 respectively). Peritoneal/liver metastases were associated with lower PFS (HR 3.6 CI95% 1.27-10.24 p 0.02 respectively). Overall, tumors with WNT pathway alterations tend to have shorter PFS and OS. Liver metastases were associated with lower OS (NR vs 34 months HR 2.49 CI95% 1.01-6.17 p 0.05). Table summarizes outcomes. Among MSS patients, median age was 57 years (41-75), with 25% female and 92% of patients receiving immunotherapy &gt; = 3rd line. Regarding tumor characteristics, 78% were left-sided and 90% harboured WNT alterations. 79%, of patients presented with liver or peritoneal metastases. WNT mutations were not associated with ORR, patients without liver/peritoneal metastases tend to have higher ORR (12.5% vs 3.3% p 0.335). Patients with WNT alterations had worse PFS (9.23 vs 1.87 months, p 0.12), and liver metastases were associated with lower PFS (6.98 vs 1.79 months HR 2.87 CI95% 1.17-7.09 p:0.02). Regarding OS, tumors harboring WNT alterations have shorter OS (8.4 vs 12 months p 0.63). The presence of liver or peritoneal metastases was associated with lower OS (NR vs 7.85 months HR 3.69 CI95% 1.09-12.55 p: 0.04). Conclusions: In our cohort, WNT pathway mutations, and liver metastases were associated with worse ORR, PFS, and OS regardless of MSI status. These findings need further validation in a prospective cohort. [Table: see text]
A peptide-based human papillomavirus therapeutic vaccine, PepCan, or <i>Candida</i> adjuvant alone in treatment of cervical intraepithelial neoplasia 2/3 (CIN2/3).
Authors: Mayumi Nakagawa, Teresa Evans, Hannah Coleman, Jasmine Crane, Nadia Darwish, Jennifer L. Faulkner, Amy Jones, Haley Kelly, Benjamin Lieblong, Yong-Chen Lu, Intawat Nookaew, Yang Ou, Charles Matthew Quick, David Ussery, Michael Scott Robeson, Sumit Shah, Takeo Shibata, Horace Spencer, Heather Williams, William Greenfield
Journal: Journal of Clinical Oncology (2023)

5538 Background: A non-surgical alternative for treating CIN2/3 would be desirable for women of childbearing age due to a risk of cervical incompetency in subsequent pregnancies following surgical treatments. PepCan consists of four current good manufacturing-grade HPV 16 E6 peptides and a Candida skin testing reagent (Candin, Nielsen Biosciences), because of Candida’s ability to regress common warts in humans, and to promote T cell proliferation and interleukin-12 secretion in vitro. Methods: In this single-center, randomized, double-blind Phase II study (NCT02481414), women with biopsy-confirmed CIN2/3 were treated with PepCan or Candida (1:1). Four intradermal injections were given 3 weeks apart which were followed with two visits 6 months apart. Histological responses (primary endpoint) were assessed using quadrant biopsies, and those whose lesions regressed to no CIN were considered to be responders. Regression rate of each treatment group was compared to that of a historical placebo group following the same treatment schedule. A sample size of 35 per arm had 93% power to test the null hypothesis that π = 0.29 (historical control placebo rate) and detect a difference of 0.31 with a two-sided type I error of 5%. Adverse events (AEs) were assessed using Common Terminology Criteria for Adverse Events Version 4. Results: Of 99 subjects screened, 81 (81.8%) qualified for vaccination, and 80 received at least one vaccination. No dose-limiting toxicity was observed. With the intention-to-treat analysis, PepCan showed 30.8% efficacy (12 of 39, p=0.16) while Candida demonstrated 47.6% efficacy (20 of 42, p=0.0004). Likewise, with the per-protocol analysis, PepCan showed 45.8% efficacy (11 of 24, p=0.06) and Candida showed 62.1% efficacy (18 of 29, p=0.0002). There was no difference between efficacy of PepCan and Candida. Conclusions: PepCan and Candida treatments are safe. Only Candida was effective in inducing histological regression in the intention-to-treat and per-protocol analyses. Candida could become a new treatment for CIN2/3 by eliciting general immune stimulation similar to checkpoint inhibitors. Clinical trial information: NCT02481414 . [Table: see text]